This work was supported by the National Institutes of Health (NIH/NHLBI) [Grant no. HL114869] and the support from UTHSC to SM.

倫理の声明：このビデオ資料に記載されたすべての動物の手順を見直し、テネシー健康科学センターの大学の動物実験委員会（IACUC）によって承認されました。 注：外科的処置を通して無菌の顕微手術器具を使用してください。外科用器具は、1,500°F（815.6°C）の最適な殺菌温度で赤外線殺菌を利用して滅菌することができます。テレメータを再利用することができるが、動物に挿入する前に、製造業者の指示に従って、全体の送信機を殺菌し、カテーテルの先端は、メーカーが提供する特殊なゲルを補充されたことにしてください。 1.実験動物<ol><li>実行されるすべての実験のためのIACUCの承認を得ます。制度的IACUCとの協議は非常にこの手順後の術後の鎮痛剤使用のための要件に関する推奨します。 </li><li> （c）に動物を飼います食料と水に自由にアクセスで、21℃、相対湿度60％、周囲温度と12時間の明暗サイクルを持つlimateを制御した部屋。 注：マウス本体は、テレメトリプローブ（×2センチ近似的直径1cm）を収容しなければならないので、20 g以上の重マウスを使用することが好ましいです。 </li></ol> 2.麻酔や手術の準備<ol><li>精密スケールを用いてマウスを計量し、その重量を記録します。静かに静かに動物を処理することを確認します。 </li><li>誘導室に動物を置き、それを閉じます。 0.5 L / minで酸素流量を設定し、4でイソフルラン濃度を設定 - 5％。 </li><li> 37°C - マウスが意識を失うと、36で維持ボディ温暖化プレートの上に置きます。 2％イソフルランがセットされたノーズコーンを介して麻酔を維持する（0.5 L /分に流量を維持します）。 </li><li>首とトンの後ろから髪を除去することにより、操作領域を準備します彼脱毛クリームを適用することにより、首の腹側面。 </li><li> 70％イソプロピルアルコールで交互に手術用ス​​クラブ（ベータダイン液）の3アプリケーションとの切開部位を扱います。 </li></ol> 3.手術<ol><li>仰臥位でマウスを置きます。足をつまんで反射神経をチェックし、応答がないまで、麻酔を調整します。メスでマウスの首下約1 cmの正中切開を行います。カットの左側には慎重に下にある結合組織から皮膚を分離することにより、皮下スペースを作成します。 </li><li>マウスを裏返して、肩甲骨の後ろに背左側に約1.5 cmで皮膚切開を作るためにメスを使用しています。デバイスを収容するのに十分な大きさの動物の脇腹に沿って皮下ポケットを作成します。ポケットに送信機を挿入します。 </li><li>バック切開の小さな止血クランプを挿入し、前方に向かって皮下にそれを操縦首の開口部。挿入、止血クランプを使用して、穏やかに非毒性のポリエチレンチューブ（4センチメートル長×1ミリメートルID）を把握します。 <ol><li>チューブは両方の腹部と背部切開部から突出するまで、バックの横切開アウトトンネルを通って戻って止血剤を引き出し止血剤からチューブを解放します。背面から、首を通ってトンネルにチューブに圧力感知カテーテルの先端をカテーテルセンサーを挿入します。首の前部からは、引き、ポリエチレンチューブを除去し、金属製のクリップを使用して、背側切開部を閉じます。 </li></ol></li><li>慎重に滅菌綿棒アプリケーターを使用して、下顎腺を分離し、弾性ステーフックを使用して、左の下顎腺を撤回。先の細い湾曲した鉗子を使用して、気管の左側に頸動脈を見つけます。滅菌ドレープを配置し、固定することにより、無菌手術部位を保管してください。 <ol><li>慎重に周囲の組織から血管を分離し、静かに分離迷走神経（色は白っぽい）離れて動脈からの頸動脈に沿っています。カットまたは神経や動脈を傷つけないように注意してください。 </li></ol></li><li>孤立した頸動脈のセクションの下に7-0非吸収性縫合糸の3枚を渡します。血流を閉鎖する頭蓋縫合糸を結びます。一時的に大動脈からの血流を閉塞するために胸骨に最も近い縫合糸を引き出します。 </li><li>中央の縫合糸を使用して、緩い結び目を作ります。これは、容器内にカテーテルを固定するために使用されます。頭蓋とマイクロはさみを使用して、胸骨縫合糸の間の動脈に小さな切開をカット。 </li><li>プローブからのゲルの損失を防ぐためにカテーテルを圧迫しないように注意して、特殊な血管カニュレーション鉗子でカテーテルをつかみます。優しく、細かい先端湾曲したピンセットをピンセットで動脈をつかむカテーテルを取り出し、小さな切開を通って容器に挿入します。 </li><li>動脈の中間辺り縫合ノードを締めて、優しく猫を進めますheter。ゆっくり胸骨の近位にある縫合糸を解放し、横大動脈に向かってカテーテルを前進させ続けます。 <ol><li>カテーテルを挿入する必要がどこまでのおおよその指標を与えるカテーテル上のマークを観察します。ポイントに達すると、そっと下カテーテルの周りの上部に縫合糸の両方を締めます。カテーテルは、縫合糸の結び目によって頚動脈に固定されています。 </li></ol></li><li>非吸収性5-0縫合糸で皮膚切開を閉じます。閉じられた後は、組織接着剤で切開部をシールします。 </li></ol> 4.外科回復とBP測定<ol><li>通常の姿勢や行動の復帰のために密接に動物を監視します。スタッフの獣医師の指示通りに24時間術後期間中鎮痛を管理します。 </li><li>動物が回復したら（5から7日後に手術）、テレメトリーレシーバープレートの上に置かれ、通常のマウスのケージに個別に収容します。 </li><li>移植TRを回し簡単にケージの外から動物の近くに位置する磁気デバイスを使用して、そして「オン」と「オフ」ansmitters。 </li></ol>

<ol>
	<li>Danaei, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+preventable+causes+of+death+in+the+United+States:+comparative+risk+assessment+of+dietary,+lifestyle,+and+metabolic+risk+factors.">The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors.</a> PLoS Med. 6 (4), e1000058 (2009).</li><li>Dornas, W. C., Silva, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+for+the+study+of+arterial+hypertension.">Animal models for the study of arterial hypertension.</a> J Biosci. 36 (4), 731-737 (2011).</li><li>Henze, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persistent+alterations+in+heart+rate+variability,+baroreflex+sensitivity,+and+anxiety-like+behaviors+during+development+of+heart+failure+in+the+rat.">Persistent alterations in heart rate variability, baroreflex sensitivity, and anxiety-like behaviors during development of heart failure in the rat.</a> Am J Physiol Heart Circ Physiol. 295 (1), H29-H38 (2008).</li><li>Hoffmann, D. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+tempol+prevents+hypertension,+proteinuria,+and+poor+feto-placental+outcomes+in+BPH/5+mouse+model+of+preeclampsia.">Chronic tempol prevents hypertension, proteinuria, and poor feto-placental outcomes in BPH/5 mouse model of preeclampsia.</a> Hypertension. 51 (4), 1058-1065 (2008).</li><li>Lerman, L. O., Chade, A. R., Sica, V., Napoli, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+hypertension:+an+overview.">Animal models of hypertension: an overview.</a> J Lab Clin Med. 146 (3), 160-173 (2005).</li><li>Johns, C., Gavras, I., Handy, D. E., Salomao, A., Gavras, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Models+of+experimental+hypertension+in+mice.">Models of experimental hypertension in mice.</a> Hypertension. 28 (6), 1064-1069 (1996).</li><li>Vatner, S. F., Braunwald, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiovascular+control+mechanisms+in+the+conscious+state.">Cardiovascular control mechanisms in the conscious state.</a> N Engl J Med. 293 (19), 970-976 (1975).</li><li>Zhao, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arterial+Pressure+Monitoring+in+Mice.">Arterial Pressure Monitoring in Mice.</a> Curr Protoc Mouse Biol. 1, 105-122 (2011).</li><li>Whitesall, S. E., Hoff, J. B., Vollmer, A. P., D'Alecy, L. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+simultaneous+measurement+of+mouse+systolic+arterial+blood+pressure+by+radiotelemetry+and+tail-cuff+methods.">Comparison of simultaneous measurement of mouse systolic arterial blood pressure by radiotelemetry and tail-cuff methods.</a> Am J Physiol Heart Circ Physiol. 286 (6), H2408-H2415 (2004).</li><li>Kurtz, T. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recommendations+for+blood+pressure+measurement+in+humans+and+experimental+animals.+Part+2:+Blood+pressure+measurement+in+experimental+animals:+a+statement+for+professionals+from+the+subcommittee+of+professional+and+public+education+of+the+American+Heart+Association+council+on+high+blood+pressure+research.">Recommendations for blood pressure measurement in humans and experimental animals. Part 2: Blood pressure measurement in experimental animals: a statement for professionals from the subcommittee of professional and public education of the American Heart Association council on high blood pressure research.</a> Hypertension. 45 (2), 299-310 (2005).</li><li>Kurtz, T. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recommendations+for+blood+pressure+measurement+in+animals:+summary+of+an+AHA+scientific+statement+from+the+Council+on+High+Blood+Pressure+Research,+Professional+and+Public+Education+Subcommittee.">Recommendations for blood pressure measurement in animals: summary of an AHA scientific statement from the Council on High Blood Pressure Research, Professional and Public Education Subcommittee.</a> Arterioscler Thromb Vasc Biol. 25 (3), 478-479 (2005).</li></ol>

The authors have nothing to disclose.

埋め込み可能な無線遠隔測定は、過去10年間で大幅に改善されました。小さいプローブサイズは、動物のためのインプラントが少ない外傷なり、長時間のバッテリ寿命は、コストを削減するのに役立ち、かつ独立したテレメータ周波数は受信機間のクロストークを排除します。テレメトリーは自由に他の技術8,9によって必要とされている拘束、人間の相互作用、または麻酔の使用に関...

高血圧は間違いなく、それが1先進国と途上国の両方で主要な公衆衛生問題である、心血管疾患の主要な危険因子の一つです。実験的な高血圧症のいくつかの動物モデルは、ヒト2で観察されたもののような高血圧の応答を模倣するために開発されてきました。なかでも、歩行マウスが起源と高血圧への慢性暴露の影響をin vivo分析で可能に高血圧の進行を研究するための優れたモデルを表しています。 マウスでの血圧（BP）の監視は、高血圧や心不全3、4などの疾患の生理学および病態生理に関与するいくつかのメカニズムを解明するための研究を支援してきました。実際、マウスゲノムの操作は、高血圧5、6を研究するためのトランスジェニックまたは遺伝子標的モデルの生成は、適切な許可しました。しかし、穏やかな操作意識のあるマウスの鎮静や精神安定剤の使用は深く血圧7に影響を与えながら、潜在的に、データ収集中にアーティファクトを導入することができ興奮を誘発します。これらの態様は、特に重要であり、長期的な血圧の監視をしようとしたときに考慮に入れなければなりません。 そこマウスにおいて血圧を記録するいくつかの方法があり、現在入手可能な最も一般的な技術との比較は他8,9議論されています。しかし、血圧測定のためのAHAの推奨事項は、BPの動脈内測定は、一般的にあるため、直接時間10の長期間にわたってBPを測定する能力のために好ましいと結論付けました。動脈圧の直接測定と相まってラジオテレメトリは目を覚ましに生理機能を監視し、ストレスや環境関連のアーティファクト9、11を最小限に抑えながら、自由に実験動物を移動するための最先端の方法です。ラジオテレメトリは、自動的に複数の意識のある動物から血圧、心拍数、体温や動物の活動を収集する機能を提供しています。 この方法は多くの研究室では非常に人気が高まっていますが、マウスでのラジオテレメトリー注入は技術的に挑戦することができます。ここでは、マウスでの圧力変換器を移植する方法を示してステップバイステップのプロトコルを示しています。技術はマウス本体内にプローブの皮下に挿入することを含む、首にカテーテルチャンネルと左頸動脈を介して大動脈弓の近くに転送します。リモートで取得されたデータは、コンピュータモニタ上にライブ表示されます。データはまた、「オフライン」分析のために保存されています。

<table>
	<tbody>
		<tr>
			<td>Small animal anesthesia system</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td></td>
			<td>low-Flow small animal anesthesia system</td>
		</tr>
		<tr>
			<td>Pad warmer and mouse termometer</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td></td>
			<td>allows monitoring body temperature,&#160; and homeothermic control in small animals.</td>
		</tr>
		<tr>
			<td>Binocular Microscope</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td>KSCXTS-1121</td>
			<td>binocular body with boom stand pole and top LED.</td>
		</tr>
		<tr>
			<td>Hemostat Forceps</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td>INS750451</td>
			<td>used to clamp blood vessels or tag sutures</td>
		</tr>
		<tr>
			<td>Small metal Clips, 7mm, Stainless Steel</td>
			<td>Kent Scientific Corp, Torrington, Connecticut, USA</td>
			<td>INS750344</td>
			<td>used for skin closure</td>
		</tr>
		<tr>
			<td>Betadine solution</td>
			<td>Purdue Products L.P., Stamford, CT, USA</td>
			<td>NDC-67618-150-01</td>
			<td>10% povidone iodine topical solution</td>
		</tr>
		<tr>
			<td>Normal saline solution</td>
			<td>Abott Laboratories</td>
			<td>04930-04-10</td>
			<td>Needed for preventing tissue from drying.</td>
		</tr>
		<tr>
			<td>Nair (Hair remover lotion)</td>
			<td></td>
			<td></td>
			<td>Needed for fur removal from the site of incision/surgery.</td>
		</tr>
		<tr>
			<td>Braide silk suture</td>
			<td>Teleflex Medical OEM, Coventry, Connecticut, USA</td>
			<td></td>
			<td>Size 5.0, 6.0, 7.0</td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td></td>
			<td>2716</td>
			<td>70% ethanol for disinfection</td>
		</tr>
		<tr>
			<td>Spring scissors&#160;</td>
			<td>Fine Science Tool</td>
			<td>15000-10</td>
			<td>for minor dissection</td>
		</tr>
		<tr>
			<td>Scissors (angled to side)</td>
			<td>Fine Science Tool</td>
			<td>14063-011</td>
			<td>No. 3 handle</td>
		</tr>
		<tr>
			<td>Scalpel blade</td>
			<td></td>
			<td>2976-0</td>
			<td>No. 10</td>
		</tr>
		<tr>
			<td>Forceps (curved)</td>
			<td>Fine Science Tool</td>
			<td>11150-10</td>
			<td>for holding tissue</td>
		</tr>
		<tr>
			<td>Forceps (straight)</td>
			<td>Fine Science Tool</td>
			<td>11151-10</td>
			<td>for holding tissue</td>
		</tr>
		<tr>
			<td>Needle holder&#160;</td>
			<td>Fine Science Tool</td>
			<td>12002-12</td>
			<td>for suturing</td>
		</tr>
		<tr>
			<td>Fine needle nose Forceps</td>
			<td>Fine Science Tool</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Henry Schein&#160;Animal Health, Melville, New York, USA</td>
			<td></td>
			<td>a general inhalation anesthetic agent</td>
		</tr>
		<tr>
			<td>Sterilizer</td>
			<td>Benchmark Scientific, 116 Corporate Blvd, South Plainfield, NJ, USA</td>
			<td>B1000</td>
			<td>sterilize surgical tools&#160;in 5-10 seconds using infrared heating</td>
		</tr>
		<tr>
			<td>Gauze Pads</td>
			<td>Johnson &#38; Johnson, New Brunswick, NJ, USA</td>
			<td>JJ8513</td>
			<td>to use for wound cleaning, prepping, scrubbin or dressing.</td>
		</tr>
		<tr>
			<td>Telemetry Device</td>
			<td>Data Sciences International, St. Paul, MN, USA</td>
			<td>DSI-PA-C10</td>
			<td>to record blood pressure in freely moving mice</td>
		</tr>
		<tr>
			<td>Telemetry receiver system&#160; coumpled with a PC</td>
			<td>Data Sciences International, St. Paul, MN, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>small Tubing</td>
			<td>Instech Laboratories, Plymouth Meeting, PA USA</td>
			<td>BTPE-90</td>
			<td></td>
		</tr>
		<tr>
			<td>Vessel Cannulation Forceps, 13cm, 0.5mm OD</td>
			<td>World Precision Instruments</td>
			<td>503374</td>
			<td>special vessel cannulation forceps.</td>
		</tr>
		<tr>
			<td>Tissue adhesive</td>
			<td>3M Animal Care Products, St. Paul, MN, USA</td>
			<td>NAC No.:&#160;11380041</td>
			<td>&#160;use to close minor wounds, often eliminating the need for sutures and/or bandages</td>
		</tr>
		<tr>
			<td>Weighing scale&#160;</td>
			<td></td>
			<td>BB300</td>
			<td>&#160;Precision Analytical Laboratory Balance</td>
		</tr>
	</tbody>
</table>

long-term blood pressure measurement in freely moving mice using telemetry

新しい血管作用薬の開発中に、動脈血圧の監視は新しい提案された薬の有効性を評価するために重要です。実際、遺伝子改変マウスを用いて、新しい潜在的な治療標的の発見に焦点を当てた研究は、全身動脈圧変動の信頼性が高く、長期的評価を必要とします。現在、外来マウスでは血圧の長期的な測定値を得るためのゴールドスタンダードは、動脈カニューレ挿入を必要とする移植可能な無線送信機を使用しています。この技術は、テザリング、規制の必要性を排除する、またはデータサンプリング時の応力とアーチファクトを導入動物を麻酔します。しかし、カテーテル挿入を介したマウスにおける動脈血圧監視が原因で動脈のサイズが小さいため、むしろ挑戦することができます。ここでは、無線送信機と頸動脈cの成功皮下移植のための重要な鍵の通路を説明するためにステップバイステップガイドを提示しますマウスでの環化。我々はまた、術後の回復期間の後、自由に動くマウスから採取した長期血圧活性の例を含みます。この手順に従うことで、同時に複数の動物からの信頼性の直接的な血圧の録音が可能になります。

データは、受信機によってリモートで取得することができます。トレースは、品質管理（ 図1a）は、コンピュータ画面上に視覚化されます。このような動物ID、拡張期血圧と収縮期血圧などの詳細は、（ 図1b）に示されています。動脈BPを連続的に（24/7）を記録することができ、または短いプログラム間隔で（ すなわち 、60秒の取得時...

Watch this Scientific Journal Video about Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry at JoVE.com

Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry

テレメトリを使用して自由に動くマウスにおける長期血圧測定

The goal of this protocol is to assess systemic blood pressure in conscious freely moving mice using implantable radio-telemetry devices.

During the development of new vasoactive agents, arterial blood pressure monitoring is crucial for evaluating the efficacy of the new proposed drugs. ...

long-term-blood-pressure-measurement-freely-moving-mice-using

Research

JoVE Journal

Medicine

18.2K ビュー.  University of Tennessee Health Sciences Center. The goal of this protocol is to assess systemic blood pressure in conscious freely moving mice using implantable radio-telemetry devices.

ビデオ: Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion.

A murine model for ventilator induced lung injury is an important tool to study an acute lung injury in vivo. Here, we report an easy applicable in situ model for acute lung injury using high-pressure mechanical ventilation to induce acute failure of the lung.

マウスにおける急性肺障害を誘発するために圧力制御された換気

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged ...

医学

Epidural Intracranial Pressure Measurement in Rats Using a Fiber-optic Pressure Transducer

Elevated intracranial pressure (ICP) is a significant problem in several forms of ischemic brain injury including stroke, traumatic brain injury and cardiac arrest. This elevation may result in further neurological injury, in the form of transtentorial herniation1,2,3,4, midbrain compression, neurological deficit or increased cerebral infarct2,4. Current therapies are often inadequate to control elevated ICP in the clinical setting5,6,7 . Thus there is a need for accurate methods of ICP measurement in animal models to further our understanding of the basic mechanisms and to develop new treatments for elevated ICP.
In both the clinical and experimental setting ICP cannot be estimated without direct measurement. Several methods of ICP catheter insertion currently exist. Of these the intraventricular catheter has become the clinical 'gold standard' of ICP measurement in humans8. This method involves the partial removal of skull and the instrumentation of the catheter through brain tissue. Consequently, intraventricular catheters have an infection rate of 6-11%9. For this reason, subdural and epidural cannulations have become the preferred methods in animal models of ischemic injury. 
Various ICP measurement techniques have been adapted for animal models, and of these, fluid-filled telemetry catheters10 and solid state catheters are the most frequently used11,12,13,14,15. The fluid-filled systems are prone to developing air bubbles in the line, resulting in false ICP readings. Solid state probes avoid this problem (Figure 1). An additional problem is fitting catheters under the skull or into the ventricles without causing any brain injury that might alter the experimental outcomes. Therefore, we have developed a method that places an ICP catheter contiguous with the epidural space, but avoids the need to insert it between skull and brain. 
An optic fibre pressure catheter (420LP, SAMBA Sensors, Sweden) was used to measure ICP at the epidural location because the location of the pressure sensor (at the very tip of the catheter) was found to produce a high fidelity ICP signal in this model. There are other manufacturers of similar optic fibre technologies13 that may be used with our methodology. Alternative solid state catheters, which have the pressure sensor located at the side of the catheter tip, would not be appropriate for this model as the signal would be dampened by the presence of the monitoring screw. 
Here, we present a relatively simple and accurate method to measure ICP. This method can be used across a wide range of ICP related animal models.

A novel technique to record the pressures within the skull is described. The minimally invasive method uses a fibre-optic pressure sensing system to accurately measure intracranial pressure (ICP) in anaesthetized rats without causing significant brain trauma. The technique may be used in a wide range of experimental models.

光ファイバ圧力トランスデューサを使用したラットの硬膜外頭蓋内圧測定

Elevated intracranial pressure (ICP) is a significant problem in several forms of ischemic brain injury including stroke, traumatic brain injury and ...

Measurement of the Pressure-volume Curve in Mouse Lungs

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential phenotypic changes are best assessed by measurement of the changes in lung elasticity. To best understand specific mechanisms underlying such pathologies in mice, it is essential to make functional measurements that can reflect the developing pathology. Although there are many ways to measure elasticity, the classical method is that of the total lung pressure-volume (PV) curve done over the whole range of lung volumes. This measurement has been made on adult lungs from nearly all mammalian species dating back almost 100 years, and such PV curves also played a major role in the discovery and understanding of the function of pulmonary surfactant in fetal lung development. Unfortunately, such total PV curves have not been widely reported in the mouse, despite the fact that they can provide useful information on the macroscopic effects of structural changes in the lung. Although partial PV curves measuring just the changes in lung volume are sometimes reported, without a measure of absolute volume, the nonlinear nature of the total PV curve makes these partial ones very difficult to interpret. In the present study, we describe a standardized way to measure the total PV curve. We have then tested the ability of these curves to detect changes in mouse lung structure in two common lung pathologies, emphysema and fibrosis. Results showed significant changes in several variables consistent with expected structural changes with these pathologies. This measurement of the lung PV curve in mice thus provides a straightforward means to monitor the progression of the pathophysiologic changes over time and the potential effect of therapeutic procedures.

Here we present a protocol to simply and reliably measure the lung pressure-volume curve in mice, showing that it is sufficiently sensitive to detect phenotypic parenchymal changes in two common lung pathologies, pulmonary fibrosis and emphysema. This metric provides a means to quantify the lung&#8217;s structural changes with developing pathology.

マウス肺における圧力 - 容積曲線の測定

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential ...

Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

A complex integration of molecular and electrical signals is needed to transform a quiescent uterus into a contractile organ at the end of pregnancy. Despite the discovery of key regulators of uterine contractility, this process is still not fully understood. Transgenic mice provide an ideal model in which to study parturition. Previously, the only method to study uterine contractility in the mouse was ex vivo isometric tension recordings, which are suboptimal for several reasons. The uterus must be removed from its physiological environment, a limited time course of investigation is possible, and the mice must be sacrificed. The recent development of radiometric telemetry has allowed for longitudinal, real-time measurements of in vivo intrauterine pressure in mice. Here, the implantation of an intrauterine telemeter to measure pressure changes in the mouse uterus from mid-pregnancy until delivery is described. By comparing differences in pressures between wild type and transgenic mice, the physiological impact of a gene of interest can be elucidated. This technique should expedite the development of therapeutics used to treat myometrial disorders during pregnancy, including preterm labor.

Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

This manuscript provides a protocol for implanting telemeters in the mouse for the purpose of measuring intrauterine pressures during pregnancy.

マウス収縮圧力を測定するために子宮内テレメトリ<em&gt;インビボ</em

A complex integration of molecular and electrical signals is needed to transform a quiescent uterus into a contractile organ at the end of pregnancy. ...

Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early cardiopulmonary dysfunction is difficult to diagnose, particularly in animal models, as cardiopulmonary function is often measured invasively, requiring anesthesia. As many anesthetic agents are cardiodepressive, subtle changes in cardiovascular function may be masked. In contrast, chronic instrumentation allows for measurement of cardiopulmonary function in the awake state, so that measurements can be obtained under quiet resting conditions, without the effects of anesthesia and acute surgical trauma. Furthermore, when animals are properly trained, measurements can also be obtained during graded treadmill exercise.
Flow probes are placed around the aorta or pulmonary artery for measurement of cardiac output and around the left anterior descending coronary artery for measurement of coronary blood flow. Fluid-filled catheters are implanted in the aorta, pulmonary artery, left atrium, left ventricle and right ventricle for pressure measurement and blood sampling. In addition, a 20 G&#160;catheter is positioned in the anterior interventricular vein to allow coronary venous blood sampling.
After a week of recovery, swine are placed on a motor-driven treadmill, the catheters are connected to pressure and flow meters, and swine are subjected to a five-stage progressive exercise protocol, with each stage lasting 3 min. Hemodynamic signals are continuously recorded and blood samples are taken during the last 30 sec of each exercise stage.
The major advantage of studying chronically instrumented animals is that it allows serial assessment of cardiopulmonary function, not only at rest but also during physical stress such as exercise. Moreover, cardiopulmonary function can be assessed repeatedly during disease development and during chronic treatment, thereby increasing statistical power and hence limiting the number of animals required for a study.

Here we present a protocol to assess cardiopulmonary function in awake swine, at rest and during graded treadmill exercise. Chronic instrumentation allows for repeated hemodynamic measurements uninfluenced by cardiodepressive anesthetic agents.

豚の長期心血管運動テストのためのカテーテルの外科的配置

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early ...

Transdermal Measurement of Glomerular Filtration Rate in Mice

Transdermal analysis of glomerular filtration rate (GFR) is an established technique that is used to assess renal function in mouse and rat models of acute kidney injury and chronic kidney disease. The measurement system consists of a miniaturized fluorescence detector that is directly attached to the skin on the back of conscious, freely moving animals, and measures the excretion kinetics of the exogenous GFR tracer, fluorescein-isothiocyanate (FITC) conjugated sinistrin (an inulin analog). This system has been described in detail in rats. However, because of their smaller size, measurement of transcutaneous GFR in mice presents additional technical challenges. In this paper we therefore provide the first detailed practical guide to the use of transdermal GFR monitors in mice based on the combined experience of three different investigators who have been performing this assay in mice over a number of years.

Here we describe a protocol to measure glomerular filtration rate (GFR) in conscious, freely moving mice using a transdermal GFR monitor.

マウスにおける糸球体濾過率の経皮吸収測定

Transdermal analysis of glomerular filtration rate (GFR) is an established technique that is used to assess renal function in mouse and rat models of ...

Simultaneous Electrocardiography Recording and Invasive Blood Pressure Measurement in Rats

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. Research focusing on cardiovascular disease models, potential cardiovascular therapeutic targets or pharmaceutical agents requires assessment of systemic arterial pressure and heart rhythm changes. In situations where radio telemetry systems are not available or affordable, the technique of femoral artery cannulation is an alternative way to obtain intra-arterial pressure waveform recordings and systemic BP measurements. This technique is economical and can be performed with standard equipment in animal facilities. However, invasive arterial pressure recording requires cannulation of small arteries, which can be a challenging surgical skill. Here, we present step-by-step protocols for femoral artery cannulation procedures. Key procedures include the calibration of the data acquisition system, tissue dissection and femoral artery cannulation, and setup of the arterial cannulation system for pressure recording. Surface electrocardiography recording procedures are also included. We also present examples of BP recordings from normotensive and hypertensive rats. This protocol allows reliable direct recordings of systemic BP with simultaneous electrocardiography.

Here, we describe a setup for simultaneous recording of electrocardiography and intra-arterial blood pressure (BP) in experimental rats, which can be done with standard equipment in animal facilities and can be applied to physiological or pharmacological studies to investigate pathogenic or therapeutic mechanisms in cardiovascular medicine.

心電図の同時記録と侵襲的血圧ラットにおける測定

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. ...

Blood Collection Through Subclavian Vein Puncture in Mice

The mouse is the foremost mammalian model for studying human disease and human health. However, blood sample collection from mice is challenging in research work. Tail blood collection is a popular method when a small amount of blood sample is needed. Orbital artery could be considered if a large amount of blood is needed but this blood collection method has ethical issues. Formerly, we demonstrated the feasibility and safety of blood sample collection through subclavian vein puncture in rats, and here we investigate whether this method could be used in mice. We report that this method is safe and practical for blood collection in mice. Blood collection through the subclavian vein puncture in mice can be a convenient method in daily research works.

Here, we present a protocol to take blood samples from the subclavian vein of mice.

マウスの鎖骨下静脈穿刺による血液採取

The mouse is the foremost mammalian model for studying human disease and human health. However, blood sample collection from mice is challenging in ...

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. The baroreflex is a key homeostatic mechanism to counteract acute, short-term changes in arterial BP and to maintain BP in a relatively narrow physiological range. BP is sensed by baroreceptors located in the aortic arch and carotid sinus. When BP changes, signals are transmitted to the central nervous system and are then communicated to the parasympathetic and sympathetic branches of the autonomic nervous system to adjust HR. A rise in BP causes a reflex decrease in HR, a drop in BP causes a reflex increase in HR.
Baroreflex sensitivity (BRS) is the quantitative relationship between changes in arterial BP and corresponding changes in HR. Cardiovascular diseases are often associated with impaired baroreflex function. In various studies reduced BRS has been reported in e.g., heart failure, myocardial infarction, or coronary artery disease. 
Determination of BRS requires information from both BP and HR, which can be recorded simultaneously using telemetric devices. The surgical procedure is described beginning with the insertion of the pressure sensor into the left carotid artery and positioning of its tip in the aortic arch to monitor arterial pressure followed by the subcutaneous placement of the transmitter and ECG electrodes. We also describe postoperative intensive care and analgesic management. After a two-week period of post-surgery recovery long-term ECG and BP recordings are performed in conscious and unrestrained mice. Finally, we include examples of high-quality recordings and the analysis of spontaneous baroreceptor sensitivity using the sequence method.

The baroreflex is a heart-rate regulation mechanism by the autonomic nervous system in response to blood-pressure changes. We describe a surgical technique to implant telemetry transmitters for continuous and simultaneous measurement of electrocardiogram and blood pressure in mice. This can determine spontaneous baroreflex sensitivity, an important prognostic marker for cardiovascular disease.

意識のあるマウスにおける自発的な圧反射感受性を決定するための遠隔ECGと血圧伝達器の組み合わせの埋め込み

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. ...

Analyzing Long-Term Electrocardiography Recordings to Detect Arrhythmias in Mice

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ineffective in many patients. To improve patient care, novel and innovative therapeutic concepts causally targeting arrhythmia mechanisms are needed. To study the complex pathophysiology of arrhythmias, suitable animal models are necessary, and mice have been proven to be ideal model species to evaluate the genetic impact on arrhythmias, to investigate fundamental molecular and cellular mechanisms, and to identify potential therapeutic targets.
Implantable telemetry devices are among the most powerful tools available to study electrophysiology in mice, allowing continuous ECG recording over a period of several months in freely moving, awake mice. However, due to the huge number of data points (&gt;1 million QRS complexes per day), analysis of telemetry data remains challenging. This article describes a step-by-step approach to analyze ECGs and to detect arrhythmias in long-term telemetry recordings using the software, Ponemah, with its analysis modules, ECG Pro and Data Insights, developed by Data Sciences International (DSI). To analyze basic ECG parameters, such as heart rate, P wave duration, PR interval, QRS interval, or QT duration, an automated attribute analysis was performed using Ponemah to identify P, Q, and T waves within individually adjusted windows around detected R waves. 
Results were then manually reviewed, allowing adjustment of individual annotations. The output from the attribute-based analysis and the pattern recognition analysis was then used by the Data Insights module to detect arrhythmias. This module allows an automatic screening for individually defined arrhythmias within the recording, followed by a manual review of suspected arrhythmia episodes. The article briefly discusses challenges in recording and detecting ECG signals, suggests strategies to improve data quality, and provides representative recordings of arrhythmias detected in mice using the approach described above.

Here we present a step-by-step protocol for a semiautomated approach to analyze murine long-term electrocardiography (ECG) data for basic ECG parameters and common arrhythmias. Data are obtained by implantable telemetry transmitters in living and awake mice and analyzed using Ponemah and its analysis modules.

マウスの不整脈を検出するための長期心電図記録の分析

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ...